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, 28 (7), 1467-71

Long-term Follow-Up of Imatinib in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL0031

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Long-term Follow-Up of Imatinib in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL0031

K R Schultz et al. Leukemia.

Abstract

We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1-21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.

Figures

Figure 1
Figure 1
Comparison of disease-free survival (DFS) (Patients not in remission by the end of consolidation block 2 and those who did not complete consolidation block 2 were excluded.) for (a) Cohort 5 chemotherapy only vs ALL patients receiving a related BMT vs unrelated BMT. (b) Comparison of disease-free survival (DFS) for cohort 5 chemotherapy only versus cohort 5-treated related and unrelated BMT.
Figure 2
Figure 2
Impact of MRD on chemotherapy outcomes (a) at study entry MRD on cohort 3/4-treated patients; (b) at study entry MRD on cohort 5-treated patients and (c) end of consolidation 2 MRD in cohort 5 chemotherapy-treated patients; (d) impact of MRD at end of consolidation 2 on BMT outcomes.
Figure 3
Figure 3
Impact of additional cytogenetic abnormalities on chemotherapy outcomes in (a) cohort 3/4 and (b) cohort 5-treated patients.

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